Occupational exposure to environmental tobacco smoke.
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Humans↗
Biomedical subjects
P Reynolds
Publications and source records attributed to P Reynolds.
Differences between black and white patients with cancer of the uterine corpus in interval from symptom recognition to initial medical consultation (United States).
To determine whether Black women with symptoms of uterine corpus cancer had longer times from symptom recognition to initial medical consultation than did White women in the United States, 331 newly diagnosed patients living in Atlanta (GA), New Orleans (LA), and San Francisco/Oakland (CA) during 1985-87 were interviewed to collect information on symptoms, dates of recognition and consultation, and other factors that might affect the interval. Data were analyzed to estimate medical consultation rates and rate ratios following symptom recognition. Median recalled times between symptom recognition and consultation were 16 days for Black women and 14 days for White women. Although poverty, having no usual source of healthcare, and other factors were associated with lower consultation rates, the adjusted rate among Black women was only somewhat lower (0.87) than among White women, and the 95 percent confidence interval (CI = 0.58-1.31) was consistent with no true difference between the races. In addition, the median time to consultation for women with stage IV cancer was only 15 days longer than the time (14 days) for the women with stage I cancer. These results suggest that time from symptom recognition to initial medical consultation does not contribute importantly to the more advanced stage cancer of the uterine corpus commonly found among Black women.
Adult↗
Glycopeptide resistance in enterococci.
Glycopeptide resistance in enterococci results from the production of peptidoglycan precursors with low affinity for these antibiotics. The mobility of the resistance genes by transposition and conjugation and the ability of the resistance proteins to interfere with synthesis of normal precursors in different hosts indicate that dissemination into other bacterial species should be anticipated.
Anti-Bacterial Agents↗
Quantitative analysis of the metabolism of soluble cytoplasmic peptidoglycan precursors of glycopeptide-resistant enterococci.
Transposon Tn1546 from Enterococcus faecium BM4147 mediates high-level resistance to the glycopeptide antibiotics vancomycin and teicoplanin. Tn 1546 encodes a dehydrogenase (VanH) and a ligase (VanA) that synthesize D-alanyl-D-lactate (D-Ala-D-Lac), a D,D-dipeptidase (VanX) that hydrolyses D-Ala-D-Ala and a two-component regulatory system (VanR-VanS) that controls transcription of the vanHAX operon. Strains of Enterococcus faecalis harbouring various copy numbers of the vanRSHAX cluster were tested to determine if there was a correlation between the levels of resistance to glycopeptides, the levels of expression of the corresponding resistance genes and the relative proportions of the different cytoplasmic peptidoglycan precursors. Increased transcription of the vanHAX operon was associated with increased incorporation of D-Ala-D-Lac into peptidoglycan precursors to the detriment of D-Ala-D-Ala, and with a gradual increase in the vancomycin-resistance levels. More complete elimination of D-Ala-D-Ala-containing precursors was required for teicoplanin resistance. The VanY and VanZ proteins also encoded by Tn1546 were not effectors of the regulation of the vanHAX operon but contributed to vancomycin and teicoplanin resistance, respectively. Differences at the regulatory level accounted for phenotypic diversity in acquired glycopeptide resistance by production of D-lac-ending precursors.
Anti-Bacterial Agents↗
Epidemiologic linkage of rodent and human hantavirus genomic sequences in case investigations of hantavirus pulmonary syndrome.
Sin Nombre virus (SNV) causes the zoonotic disease hantavirus pulmonary syndrome (HPS). Its mechanisms of transmission from rodent to human are poorly understood. It is possible that specific genetic signature sequences could be used to determine the probable site of each case-patient's exposure. Environmental assessments suggested 12 possible sites of rodent exposure for 6 HPS patients. Rodents were captured at 11 of the 12 sites and screened for SNV infection within 2 weeks of the patient's diagnosis. Viral sequences amplified from tissues of rodents at each site were compared with those from case-patients' tissues. Rodents bearing viruses with genetic sequence identity to case-patients' viruses across 2 genomic segments were identified in 4 investigations but never at >1 site. Indoor exposures to rodents were especially common at implicated sites. By distinguishing among multiple possible sites of exposure, viral genotyping studies can enhance understanding of the conditions associated with infection by SNV.
Animals↗
Should pregnancy testing be routine in adolescent patients prior to surgery?
The reliability of the preoperative history obtained from adolescent patients in ruling out pregnancy was prospectively evaluated. Four hundred forty-four patients who underwent 525 procedures were questioned preoperatively regarding the possibility of pregnancy. Regardless of the history, a urine pregnancy test was ordered in accordance with institutional practice. In 508 cases, patients denied the possibility of pregnancy. Eight patients stated that they might be pregnant, and in six cases the parents responded for the patients and denied the possibility of pregnancy. Seventeen patients were not tested due to patient/parent refusal (n = 9) or inability to void (n = 8). All pregnancy tests were negative except one that was questionably negative. This patient had denied the possibility of pregnancy and had been anesthetized prior to test results. Follow-up revealed that the patient was not pregnant. Our data demonstrate that the preoperative history obtained from adolescent patients at our institution regarding their pregnancy status was in agreement with pregnancy test results. We suggest that a detailed history regarding last menstrual period, contraception, sexual activity, and the possibility of pregnancy be obtained in all postmenarchal patients presenting for surgery. Although in other populations history and pregnancy testing did not agree 100% of the time, for our adolescent population, human chorionic gonadotrophin (HCG) testing appears to be necessary only if indicated by patient history.
Adolescent↗
Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States.
The authors conducted a population-based case-control study of lung cancer in nonsmoking women in five metropolitan areas of the United States between December 1, 1985, and November 30, 1990. In-person interviews were conducted with 412 lung cancer cases and 1,253 population controls, yielding information on history of nonmalignant lung diseases that were diagnosed by a physician. When lung cancer cases were compared with controls, history of any previous lung disease was associated with a significant increased risk of lung cancer (adjusted odds ratio (AOR) = 1.56, 95% confidence interval (CI) 1.2-2.0). Several lung diseases, including asthma, chronic bronchitis, pneumonia, and tuberculosis, were reported more often by lung cancer cases than by controls, and the difference was statistically significant for asthma (AOR = 1.67, 95% CI 1.1-2.5) and chronic bronchitis (AOR = 1.60, 95% CI 1.1-2.4). Since significant increased risks were observed for asthma and tuberculosis diagnosed before age 21 years, it is unlikely that reported prior lung diseases were prediagnostic manifestations of lung cancers. The increased risks associated with previous lung disease were observed for adenocarcinomas and other carcinomas of the lung; the point estimates were generally higher for the latter category. The risks associated with previous lung diseases remained unchanged after adjustment for potential confounders, including environmental tobacco smoke exposure during childhood and adult life and dietary factors.
Adenocarcinoma↗
The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin.
A five-gene cluster from Tn1546 confers resistance to the glycopeptide antibiotics vancomycin (Vm) and teicoplanin (Te) by synthesis of pentadepsipeptide peptidoglycan precursors terminating in D-lactate, which replaces D-alanine in the same position of precursors utilized by susceptible enterococci. Cloning and nucleotide sequencing indicated that Tn1546 contains an additional gene, designated vanZ, which confers low-level Te resistance, in the absence of the genes required for pentadepsipeptide synthesis. Analysis of cytoplasmic peptidoglycan precursors, accumulated in the presence of ramoplanin, showed that VanZ-mediated Te resistance does not involve incorporation of a substituent of D-alanine into the precursors.
Amino Acid Sequence↗
Anatomic site distribution of colon cancer by race and other colon cancer risk factors.
PURPOSE: Black patients with colon cancer are more likely to have poorer survival from colon cancer than are white patients. To determine whether anatomic site differences might contribute to survival differences, we compared anatomic site distributions of black and white patients. METHODS: As part of the Black/White Cancer Survival Study, we collected medical record data for 1,045 patients from Atlanta, New Orleans, and San Francisco/Oakland, newly diagnosed in 1985 or 1986 and interviewed 745 of them. RESULTS: In polychotomous logistic regression analysis, site was related to stage, grade, and histologic type and among women with age, parity, and possibly smoking. However, it was not related to race, except perhaps among men age 65 and older, among whom blacks were somewhat likely to have more transverse and distal, not proximal, cancer. These relations were consistent across subgroups and were independent of other factors examined. CONCLUSION: Results suggest that site differences are unlikely to contribute to poorer survival commonly observed among black colon cancer patients in the United States.
Adult↗
The cerebral function monitor (CFM) is a useful addition to a bilateral carotid artery, vein graft model.
Following human coronary artery bypass surgery, vein graft occlusion is a major cause of morbidity and mortality. An agent is required which will reduce the incidence of early graft thrombosis without causing systemic bleeding. To assess the efficacy of such agents a suitable experimental vein-graft model is required. A porcine, unilateral saphenous vein-carotid artery bypass graft model has been described previously, although to assess the effect of locally applied anticoagulant drugs, insertion of grafts bilaterally would be advantageous, allowing treated and control grafts to be implanted in the same animal which would then act as its own control. Pigs are reported as having an excellent collateral cerebral circulation and hence in theory, would be suitable animals to use as a bilateral carotid vein-graft model. This paper describes the occurrence of serious neurological complications during the development of such a model and suggests that by using a cerebral function monitor, detection of critical reductions in cerebral perfusion can be made early and remedial action take.
Animals↗
Passive smoking and lung cancer.
Evidence that environmental tobacco smoke may be a risk factor for lung cancer among individuals who themselves have never smoked tobacco products has been the subject of expert review over the last decade by several United States and international agencies. The most recent comprehensive review, published in 1993 by the United States Environmental Protection Agency, concluded that environmental tobacco smoke is a Group A (known human) carcinogen. This report, coming in the midst of rapid social and political change in attitudes towards public policy implications for protecting human health, has been the subject of considerable discussion. Issues involved in these discussions, as well as more recently published studies on the topic, are reviewed with respect to current thinking about the risk of lung cancer in passive smokers, particularly women, who are lifetime never-smokers.
Epidemiologic Factors↗
Effect of intraluminal application of tissue-type plasminogen activator on the fibrinolytic activity of experimental vein grafts.
OBJECTIVE: The aim was to quantify the effect of intraluminally applied tissue-type plasminogen activator (tPA) on the fibrinolytic activity of experimental vein grafts and assess the effect of pretreatment of the vein on early platelet and thrombus formation using histological techniques. METHODS: A pig model of bilateral saphenous venin-carotid artery grafts was used. In each animal one side of the neck was grafted using vein distended to 230 mm Hg and pretreated with tPA (1 mg.ml-1) for a period of 15 min before grafting (treated graft). The perfused in situ for 2 h after implantation and before analysis. Changes in local fibrinolytic activity were quantified using fibrin plate techniques and specific chromogenic assays for tPA and urokinase (uPA) in tissue extract (n = 6 animals). Histological assessment was made using light and scanning microscopy (n = 4 animals). RESULTS: Surgical preparation and distention significantly reduced the fibrinolytic activity of pig saphenous vein in terms of areas of lysis produced on fibrin plates (P < 0.05), tPA activity (P < 0.05), and uPA activity (P < 0.05). Pretreatment of distended vein with tPA before grafting significantly enhanced its fibrinolytic activity after 2 h perfusion compared to control (untreated) grafts, as assessed by areas of lysis on fibrin plates (P < 0.05) and specific tPA activity (P < 0.05). Treated grafts also showed qualitatively less platelet and thrombus formation on histological examination. CONCLUSIONS: Pretreatment of surgically harvested vein by intraluminal application of tPA before grafting enhances its fibrinolytic activity after exposure to 2 h perfusion in vivo. This technique requires further investigation to validate its potential as a means of providing local anticoagulation to veins implanted as arterial grafts thereby reducing the incidence of early graft thrombosis.
Animals↗
Antigen presentation and assembly by mouse I-Ak class II molecules in human APC containing deleted or mutated HLA DM genes.
The behavior of mouse I-Ak molecules was studied in the human Ag presentation mutants T2 and 9.5.3, which contain deleted or mutated HLA DM genes. HLA class II molecules expressed by these APC are defective in presentation of native Ag and are mostly complexed with class II-associated invariant chain peptides (CLIP). In contrast to human class II molecules, a significant proportion of mouse I-Ak molecules expressed in T2 and 9.5.3 were associated with antigenic peptides, indicating that I-Ak/peptide assembly is possible in the absence of the Dm proteins. Thus, the presentation of determinants derived from hen egg lysozyme (HEL), keyhole limpet hemocyanin, and conalbumin was normal in 9.5.3Ak and a conalbumin determinant was presented normally by T2.Ak. However, the keyhole limpet hemocyanin determinant was not presented by T2.Ak, and HEL46-61 was only presented at a low level by these APC. SDS-stable, dimeric I-Ak molecules were expressed by both T2.Ak and 9.5.3Ak and formed late in their intracellular transport. Presentation of HEL46-61 was partially inhibited by disrupting vacuolar acidification in 9.5.3Ak, consistent with I-Ak/peptide assembly in a post-Golgi endosomal compartment. Accordingly, Dm is not an obligatory requirement for MHC class II/peptide assembly. We propose that Dm influences the displacement of CLIP from recently synthesized class II molecules, a process that is likely to be less critical for I-Ak because of its low affinity for CLIP.
Animals↗
Environmental tobacco smoke and lung cancer in nonsmoking women. A multicenter study.
OBJECTIVE: To determine the relative risk (RR) of lung cancer in lifetime never smokers associated with environmental tobacco smoke (ETS) exposure. DESIGN: Multicenter population-based case-control study. SETTING: Five metropolitan areas in the United States: Atlanta, Ga, Houston, Tex, Los Angeles, Calif, New Orleans, La, and the San Francisco Bay Area, Calif. PATIENTS OR OTHER PARTICIPANTS: Female lifetime never smokers: 653 cases with histologically confirmed lung cancer and 1253 controls selected by random digit dialing and random sampling from the Health Care Financing Administration files for women aged 65 years and older. MAIN OUTCOME MEASURE: The RR of lung cancer, estimated by adjusted odds ratio (OR) with 95% confidence interval (CI), associated with ETS exposure. RESULTS: Tobacco use by spouse(s) was associated with a 30% excess risk of lung cancer: all types of primary lung carcinoma (adjusted OR = 1.29; P < .05), pulmonary adenocarcinoma (adjusted OR = 1.28; P < .05), and other primary carcinomas of the lung (adjusted OR = 1.37; P = .18). An increasing RR of lung cancer was observed with increasing pack-years of spousal ETS exposure (trend P = .03), such that an 80% excess risk of lung cancer was observed for subjects with 80 or more pack-years of exposure from a spouse (adjusted OR = 1.79; 95% CI = 0.99 to 3.25). The excess risk of lung cancer among women ever exposed to ETS during adult life in the household was 24%; in the workplace, 39%; and in social settings, 50%. When these sources were considered jointly, an increasing risk of lung cancer with increasing duration of exposure was observed (trend P = .001). At the highest level of exposure, there was a 75% increased risk. No significant association was found between exposure during childhood to household ETS exposure from mother, father, or other household members; however, women who were exposed during childhood had higher RRs associated with adult-life ETS exposures than women with no childhood exposure. At the highest level of adult smoke-years of exposure, the ORs for women with and without childhood exposures were 3.25 (95% CI, 2.42 to 7.46) and 1.77 (95% CI, 0.98 to 3.19), respectively. CONCLUSION: Exposure to ETS during adult life increases risk of lung cancer in lifetime nonsmokers.
Aged↗
How does autoimmunity to La and Ro initiate and spread?
Autoimmunity to La(SS-B) and Ro(SS-A) is a paradigm for understanding the normal mechanisms of B cell and T cell tolerance and development of autoimmunity to clinically important sequestered autoantigens. Epitope mapping experiments have indicated that the autoantibody response is largely self antigen-driven but have failed to elucidate why these particular autoantigens are selected. Abnormal trafficking of La or Ro peptides in polarised epithelial cells and their presentation to autoreactive T cells, or selective release of ribonucleoproteins by injured epithelial cells, could explain the targeting of salivary and lacrimal epithelium in Sjogren's syndrome. There appears to be little, if any, immune tolerance to La in the T helper and B cell compartments. Both intra-and inter-molecular spreading of the autoimmune response have been observed for La. We present a model of recruited autoimmunity whereby capture and internalisation of La/Ro ribonucleoproteins by B cells and subsequent presentation of La or Ro determinants to autoreactive T cells could lead to inter-molecular spreading of the response.
Autoantigens↗
Purification and characterization of the Saccharomyces cerevisiae RAD1/RAD10 endonuclease.
The Saccharomyces cerevisiae RAD1 and RAD10 genes are required for the incision step of excision repair, and in addition, they function in mitotic recombination. The RAD1 and RAD10 proteins are associated in a tight complex, and genetic studies have indicated that complex formation is essential for the RAD1/RAD10 controlled biological activities. We had previously purified the RAD10 protein to near homogeneity from yeast and shown that it is a DNA-binding protein with a strong preference for single-stranded DNA. In this study, we purify the RAD1 protein to near homogeneity from yeast and show that it also binds single-stranded DNA preferentially and that the RAD1/RAD10 complex possesses an endonuclease activity. We characterize the RAD1/RAD10 endonuclease activity on both single-stranded and double-stranded DNAs, using agarose gel electrophoresis and trichloroacetic acid precipitation. The RAD1/RAD10 nuclease exhibits a much higher level of activity on single-stranded DNA than double-stranded DNA. The susceptibility of double-stranded DNA to nicking by the RAD1/RAD10 enzyme is markedly dependent on the degree of negative superhelicity, such that a 15-fold increase in nicking rate is observed from superhelical state sigma = zero to sigma = -0.08. The enzyme produces 3'-hydroxyl and 5'-phosphate termini on both single- and double-stranded DNAs. We discuss the role of RAD1/RAD10 endonuclease in nucleotide excision repair and in mitotic recombination.
Chromatography, Ion Exchange↗
The spectrum of acquired immunodeficiency syndrome (AIDS)-associated malignancies in San Francisco, 1980-1987.
Population-based disease registries for acquired immunodeficiency syndrome (AIDS) and cancer were linked for San Francisco residents to study the pattern of AIDS-associated malignancies diagnosed during the time period 1980-1987. A total of 1,756 newly diagnosed malignancies were identified during these years among members of the AIDS cohort. Of these, 1,752 (99.7%) occurred in males, 1,454 (83%) were Kaposi's sarcoma, 235 (13%) were non-Hodgkin's lymphoma, and 16 (1%) were Hodgkin's disease. The distributions of AIDS patients with cancer differed significantly from those without cancer by race and by risk group. Malignancies known to be human immunodeficiency virus (HIV)-associated, and now diagnostic of AIDS (Kaposi's sarcoma, non-Hodgkin's lymphoma), were, as would be expected, dramatically in excess among AIDS patients. Some malignancies not traditionally thought to be HIV-associated appear to have occurred more often than expected in the study cohort. These include Hodgkin's disease, rare non-melanoma skin cancers, and cancers of the rectum, anus, and nasal cavity. Malignancies known to be HIV-associated were more likely to be diagnosed concurrent with or subsequent to first AIDS diagnosis. Conversely, malignancies not known to be HIV-associated were more likely to be diagnosed before AIDS diagnosis. Compared with the concurrent reference population of the San Francisco Bay Area, there was little or no increase in Kaposi's sarcoma over the time interval of this study. For non-Hodgkin's lymphoma, and suggestively for Hodgkin's disease, however, the temporal increase has been quite dramatic.
Acquired Immunodeficiency Syndrome↗
Expression and functional conservation of the human La (SS-B) nuclear autoantigen in murine cell lines.
We have studied the cellular expression and functional conservation of the human La autoantigen across species by introducing genes encoding human La antigen into cultured murine cell lines. In transfected murine fibroblasts and lymphoid cell lines human La was expressed as a predominantly nuclear antigen, with a typical pattern of nuclear speckling. Radiolabeled human La was of the predicted molecular mass (48 kDa) when expressed in murine cells and was associated intracellularly with murine 60 kDa Ro antigen. Under certain conditions of cell lysis the association between human La and murine Ro was disrupted, whereas human La and human Ro complexes remained intact, suggesting the possibility of species-specific protein interaction between La/Ro antigens. Expression of human La from the genomic gene construct was associated in some transfectants with the presence of additional high molecular weight bands reactive with anti-La monoclonal antibodies. Cell surface La determinants were not detected on any of the transfected cells. Human La protein associated with many of the same radiolabeled RNAs as the murine La antigen in transfected murine cells, indicating intact RNA-binding function of La protein across species. The findings indicate that despite 23% non-identity within the primary structure of human and murine La, the human molecule is functionally highly conserved across species.
Animals↗